A preventive program for control of a severe X-linked form of cerebral palsy, the Lesch-Nyhan syndrome, has come from recent progress in our understanding of its basic genetic and biochemical cause. The feasibility of prenatal diagnosis using cultured amniotic cells and gestational management has been demonstrated by identification of six affected males in eighteen pregnancies at risk for the disease and monitored during the past seven years. In each instance the diagnosis was made sufficiently early that the parents' desire to terminate the pregnancy could be met. This demonstration makes imperative the eventual identification of all affected patients in various high risk groups. In this way the female relatives at risk for carrying this X-linked gene can be alerted to the need for monitoring their pregnancies if they are to avoid producing affected children. The objective is to demonstrate in a pilot program the applicability of this approach to preventive control and to evaluate the relative effectiveness of screening various population groups in identifying new patients with this disease and through them, the female carriers of the gene. A simple automated urine screening test based on the high ratio of uric acid to creatinine in morning urine samples blotted onto filter paper, dried and sent to our laboratory for analysis will identify affected patients from among 100,000 patients in cerebral-palsy clinics, neurology clinics, schools for the handicapped and mental hospitals of California, Arizona, Texas, Michigan and Utah. The diagnosis will be confirmed in each case by an enzyme assay on erythrocytes and collection, where possible, of a 24-hour urine. Pedigrees will be obtained and heterozygous females identified. The program outlined is limited in scope and time to the size of survey needed to identify the most effective mechanism for carrying out the objective. We anticipate that it will serve as a model for use by state health departments after we publish the frequency of new cases found in the various groups tested.